Keratinization is a specialized and orderly differentiation process which commences in keratinocytes no longer engaged in cell division. While structural characteristics of each stage of keratinization at both light and electron microscopic levels have been documented comprehensively, chemical and functional aspects of the morphologic hallmarks require further investigation in order to advance our scientific understanding of normal and abnormal keratinization. In this project, chemical properties of nuclear proteins wich result in morphological abnormalities of the nucles in epidermal cells will be investigated by immunoelectron microscopy. How the distribution of nuclear proteins changes in epidermal cells undergoing normal and pathological keratinization will be analyzed. Similarly, immunohistochemical techniques will be used to dissect, at the chemical and molecular levels, individual constituents of submicroscopic structures such as keratohyalin granules, keratinosomes, desmosome complexes, etc. Questions to be asked include: a) where do these molecules localize in cells at different degree of maturation, and b) how do they change under pathological circumstances. The roles of epidermal enzymes in the hydrolysis of proteins in the differentiation of the nucleus and cytoplasm will also be determined biochemically. Protein products resulting from both limited proteolysis and interactions of enzymes and inhibitors will be demonstrated. Finally, bioactivities of proteins in differentiated keratinocytes will be elucidated as enzyme regulators and/or anti-microbial agents. The methodology and basic information obtained in normal skin will be applied to diseases such as psoriasis, ichthyosis and verrucae. The resulting information will be utilized to improve understanding of pathomechanisms of the diseases.